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The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress

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Abstract

Stress is considered as an important risk factor in the progression and the onset of many disorders such as multiple sclerosis. However, metabolite changes as a result of demyelination under the detrimental effects of stress are not well understood. Thus, 36 female Wistar rats (i.e., groups (1) no-cuprizone (Cont), (2) no-stress + cuprizone-treated (Cup), (3) physical stress + cuprizone-treated (P-Cup), (4) psychological stress + cuprizone-treated (Psy-Cup), (5) physical stress + no-cuprizone-treated (P), (6) psychological stress + no-cuprizone-treated (Psy)) were used in this study. Following induction of repetitive stress, cuprizone treatment was carried out for 6 weeks to instigate demyelination in all groups except the control animal. Relative metabolite concentrations of the brain were investigated by single-voxel proton magnetic resonance spectroscopy (reporting N-acetyl-aspartate (NAA), glycerophosphocholine with phosphocholine (tCho) relative to total creatine (tCr)). According to 1H-MRS, rats in the Cup group indicated a reduction in NAA/ tCr (p < 0.001) as well as tCho/ tCr (p < 0.05) compared with that in the Cont group. In contrast, in both stress + cuprizone-treated groups, NAA/tCr and tCho/tCr ratios remarkably increased versus the Cup group (p < 0.001) and the Cont group (p < 0.001 for the Psy-Cup group and p < 0.05 for the P-Cup group). Both P and Psy groups revealed normal metabolite concentrations similar to the Cont group 6 weeks post stress. Seemingly, in the case of cuprizone alone, decreased level of metabolites is mainly relevant to neuronal cell impairments. Meanwhile, as a result of oxidative stress enhancement due to stress exposure, oligodendrocyte becomes the main victim indicating the increased level of metabolite ratios.

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Acknowledgments

The authors would like to acknowledge the Iranian National Brain Mapping Laboratory (NBML), Tehran, Iran, for MRS acquisition.

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Authors and Affiliations

  1. Laboratory of Neuro-Organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

    Sogol Meknatkhah, Monireh-Sadat Mousavi & Gholam Hossein Riazi

  2. College of Engineering, Faculty of Chemical Engineering, University of Tehran, Tehran, Iran

    Pouya Sharif Dashti

  3. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Samira Raminfard

  4. Quantitative Medical Imaging Systems Group (QMISG) Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran

    Hamidreza Saligheh Rad

  5. Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

    Hamidreza Saligheh Rad

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  1. Sogol Meknatkhah
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  4. Hamidreza Saligheh Rad
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  5. Monireh-Sadat Mousavi
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  6. Gholam Hossein Riazi
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Correspondence to Gholam Hossein Riazi.

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ECPII (Ethical Committee of the Pasteur Institute of Iran) approved all experimental procedures and efforts were made to minimize the suffering and to reduce the number of the rats used.

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Meknatkhah, S., Dashti, P.S., Raminfard, S. et al. The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress. J Mol Neurosci 71, 804–809 (2021). https://doi.org/10.1007/s12031-020-01702-9

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  • DOI: https://doi.org/10.1007/s12031-020-01702-9

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